Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTS5K1M)

• DTT Name: Hepatitis B virus Reverse transcriptase (HBV RT)
• Synonyms: P; HBV reverse transcriptase
• Gene Name: HBV RT
• DTT Type: Successful target; [1]
• BioChemical Class: DNA-directed DNA polymerase
• UniProt ID: DPOL_HBVA3
• TTD ID: T56518
• EC Number: EC 2.7.7.49
• Sequence:
  EHHIRIPRTPARVTGGVFLVDKNPHNTAESRLVVDFSQFSRGISRVSWPKFAVPNLQSLT
  NLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLIGSSGLSRYVARLSSNSRINNNQYGTMQ
  NLHDSCSRQLYVSLMLLYKTYGWKLHLYSHPIVLGFRKIPMGVGLSPFLLAQFTSAICSV
  VRRAFPHCLAFSYMDDVVLGAKSVQHRESLYTAVTNFLLSLGIHLNPNKTKRWGYSLNFM
  GYII
• Function: Multifunctional enzyme that converts the viral RNA genome into dsDNA in viral cytoplasmic capsids. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3'- to 5'-endonucleasic mode. Neo-synthesized pregenomic RNA (pgRNA) are encapsidated together with the P protein, and reverse- transcribed inside the nucleocapsid. Initiation of reverse- transcription occurs first by binding the epsilon loop on the pgRNA genome, and is initiated by protein priming, thereby the 5'- end of (-)DNA is covalently linked to P protein. Partial (+)DNA is synthesized from the (-)DNA template and generates the relaxed circular DNA (RC-DNA) genome. After budding and infection, theRC- DNA migrates in the nucleus, and is converted into a plasmid-like covalently closed circular DNA (cccDNA). The activity of P protein does not seem to be necessary for cccDNA generation, and is presumably released from (+)DNA by host nuclear DNA repair machinery.

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Adefovir Dipivoxil	DMMAWY1	Hepatitis B virus infection	1E51.0	Approved	[2]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clevudine	DMR21Q3	Hepatitis B	1E51	Phase 3	[3]
LB80380	DMJM9LZ	Hepatitis B virus infection	1E51.0	Phase 2b	[4]
MIV-210	DM2NF6X	Hepatitis B virus infection	1E51.0	Phase 2	[5]
Pradefovir	DM1O0DV	Hepatitis virus infection	1E50-1E51	Phase 2	[6]

References

• [1] Effect of hepatitis B virus reverse transcriptase variations on entecavir treatment response. J Infect Dis. 2014 Sep 1;210(5):701-7.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] 2011 Pipeline of Bukwang.
• [4] 2011 Pipeline of LG Life Sciences.
• [5] Emerging antivirals for the treatment of hepatitis B
• [6] DOI: 10.1128/AAC.01566-05